There have been a number of similar questions, may of which I originally had, so I created this Q&A. I've loaded the ASX announcements into OptheaGPT. While AI hallucination occur, I've reviewed the information as best I can. However, please read through it and suggest any improvements to make the Q&A more effective for newcomers.
Company Info
Q A1: Where is Opthea Limited headquartered, and when was it started?
A: Opthea Limited is headquartered in Melbourne, Australia, with a presence in Princeton, New Jersey, USA. The company was founded in 1984 as Circadian Technologies Limited and rebranded as Opthea Limited in 2015.
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Q A2: What was Circadian Technologies focused on before 2015?
A: Circadian Technologies focused on biotechnology and life sciences, particularly cancer and angiogenesis research. The company developed therapies targeting vascular endothelial growth factors (VEGF) for cancer treatment, laying the foundation for Opthea’s focus on retinal diseases.
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Q A3: What is the role of Opthea's Medical Advisory Board, and who are its members?
A: Opthea’s Medical Advisory Board (MAB) consists of 10 renowned retina experts, chaired by Dr. Arshad M. Khanani (USA). Members include Dr. David S. Boyer (USA), Prof. Andrew Chang (Australia), Prof. Frank G. Holz (Germany), Prof. Anat Loewenstein (Israel), Dr. Dante Pieramici (USA), Dr. Carl Regillo (USA), Dr. Patricio G. Schlottmann (Argentina), Prof. Tien Y. Wong (China), and Prof. Eric Souied (France). The MAB advises Opthea on strategic directions and development efforts, enhancing the company’s credibility and bolstering FDA approval chances.
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Q A4: Who are the key C-suite executives and medical officers at Opthea?
A: Key executives include Dr. Frederic Guerard, PharmD (Chief Executive Officer), Megan Baldwin, PhD (Founder and Chief Scientific Officer), David Muller (Chief Financial Officer), and Dr. Arshad M. Khanani, MD, MA, FASRS (Chief Medical Advisor).
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Q A5: What is the ticker symbol for Opthea, and where is it listed?
A: Opthea is listed on the Australian Securities Exchange (ASX) under the ticker symbol OPT. It is also listed on the Nasdaq Global Select Market in the U.S. under the ticker OPT. One Nasdaq OPT share is equivalent to eight shares of OPT on the ASX.
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Q A6: What is OPTOA?
A: OPTOA represents options for shares in Opthea Limited with an exercise price of A$0.80 per share, expiring on September 30, 2025. Approximately 98 million OPTOA options were issued, potentially raising A$78.4 million if fully exercised.
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Q A7: What is OPTOB?
A: OPTOB represents another series of options with an exercise price of A$1.00 per share, expiring on June 30, 2026. Approximately 189.4 million OPTOB options were issued, potentially raising A$189.4 million if fully exercised.
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Q A8: What are the key dates and share numbers for Opthea's capital raisings?
A: Opthea conducted a significant capital raising in September 2023, issuing approximately 160 million shares to institutional investors and 16 million shares to retail investors at an offer price of A$0.46 per share, raising a total of A$82 million. This was followed by another capital raising in June 2024, which included a Placement and an Institutional Entitlement Offer raising approximately A$171.5 million (US$113.2 million), with a retail component expected to raise an additional A$55.9 million (US$36.9 million). Combined, these funds are critical for funding the ongoing development and trials of Sozinibercept (OPT-302). Further capital raising may be required by 2026 to support the FDA approval process and potential commercialization as outlined in A10.
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Q A9: What is the Development Funding Agreement (DFA) with Carlyle/Abingworth?
A: Opthea entered into a Development Funding Agreement (DFA) with Carlyle/Abingworth in August 2022 and amended it in December 2023. The agreement provided US$170 million in non-equity funding for the development of Sozinibercept for wet AMD. Repayment is capped at US$680 million (4x the funded amount), resulting in a 300% gain for Carlyle/Abingworth if all repayment conditions are met. Repayments are split into fixed payments of US$113.33 million annually over six years, along with variable payments at 7% of net revenues. No repayment is required if the clinical trials fail or if regulatory approval is not received.
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Q A10: Will another capital raising (CR) be needed?
A: If the COAST trial achieves positive results in early Q2 2025, and Opthea moves forward with the rolling BLA submission to the FDA as outlined in C5 of the Trial Info table, it is likely that another capital raising will be required by 2026. This additional funding would be needed to support the approval process, potential commercialization, and any further repayments under the Development Funding Agreement (DFA).
Trial Info
Q C1: What is the current status of Sozinibercept (OPT-302)?
A: Sozinibercept (OPT-302) is in pivotal Phase 3 trials, including the COAST and SHORE studies, which are focused on treating wet AMD. COAST completed enrollment in February 2024 with 998 patients, and SHORE completed enrollment in May 2024 with 986 patients. Top-line data (TLD) for the 52-week safety and efficacy results are expected in early Q2 2025 for COAST and mid-2025 for SHORE. The trials particularly focus on patient sub-groups that represent approximately 75% of the wet AMD population, where Sozinibercept showed a significant benefit of +5.7 letters in BCVA at 24 weeks during Phase 2b trials.
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Q C2: What is COAST?
A: COAST is one of the Phase 3 clinical trials evaluating Sozinibercept (OPT-302) for the treatment of wet AMD. The name COAST is derived from Combination therapy with OPT-302, Aflibercept (Eylea), and Standard Treatment. The trial completed enrollment in February 2024 with 998 patients. Top-line data is expected in early Q2 2025. The primary endpoint will focus on a sub-group of patients who demonstrated the highest benefit in visual acuity (BCVA) during earlier trials, enhancing the likelihood of Phase 3 success.
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Q C3: What is SHORE?
A: SHORE is another Phase 3 clinical trial for Sozinibercept (OPT-302), similar to COAST, focusing on patients with wet AMD. The name SHORE comes from Standard therapy with High-dose OPT-302 Optimized for Retinal Evaluation. SHORE completed enrollment in May 2024 with 986 patients. Top-line data is expected in mid-2025. Like COAST, SHORE also emphasizes the same patient sub-group to increase the probability of Phase 3 success.
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Q C4: What were the results of the Phase 2b trial of Sozinibercept (OPT-302)?
A: The Phase 2b trial involved 366 participants and was conducted over 6 months. Sozinibercept (OPT-302) was co-administered with ranibizumab (Lucentis). The trial demonstrated a statistically significant improvement in visual acuity, with a P-value of 0.0107, indicating the efficacy of Sozinibercept (OPT-302) when combined with Lucentis. It is important to note that this trial did not test Sozinibercept in combination with Eylea (aflibercept). The Phase 2b trial also highlighted a +5.7 letter improvement in BCVA at 24 weeks for a sub-group representing around 75% of wet AMD patients, which is the focus of the ongoing Phase 3 trials.
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Q C5: What is the significance of Fast Track Designation for Sozinibercept?
A: Sozinibercept (OPT-302) has received Fast Track Designation from the U.S. FDA, which can accelerate the review process. Assuming positive top-line data from the COAST trial in early Q2 2025, Opthea could begin a rolling Biologics License Application (BLA) submission as early as Q3 2025. The rolling submission allows Opthea to submit completed sections of the BLA as they are ready. The BLA submission could be completed by early 2026, with potential FDA approval by mid to late 2026, allowing Sozinibercept to enter the U.S. market shortly thereafter. This accelerated timeline is contingent on the success of the COAST trial and the FDA's review process.
Background Science
Q B1: What are VEGF inhibitors and VEGF traps?
A: VEGF inhibitors are drugs designed to block the action of Vascular Endothelial Growth Factor (VEGF), a protein that promotes the growth of new blood vessels. VEGF traps are a type of VEGF inhibitor that binds VEGF molecules and prevents them from interacting with their natural receptors. By inhibiting VEGF, these drugs help reduce abnormal blood vessel growth and leakage in retinal diseases such as wet AMD. Common examples include Eylea (aflibercept), which acts as a VEGF trap.
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Q B2: What is the significance of VEGF-C and VEGF-D in retinal diseases?
A: VEGF-C and VEGF-D are members of the VEGF family that are involved in the formation of lymphatic and blood vessels. In the retina, these factors can contribute to abnormal blood vessel growth and fluid leakage, similar to VEGF-A. Sozinibercept (OPT-302) targets VEGF-C and VEGF-D in addition to VEGF-A, providing a broader inhibition of the pathways responsible for the progression of retinal diseases like wet AMD.
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Q B3: What is RAP, and why is it significant in retinal disease treatment?
A: Retinal Angiomatous Proliferation (RAP) is a subtype of wet AMD characterized by the growth of new blood vessels from the retina into the subretinal space. RAP is often more difficult to treat and is associated with worse visual outcomes. Because of its complexity, certain clinical trials, like Opthea’s Phase 3 trials for Sozinibercept, exclude patients with RAP to better assess the drug’s efficacy in the broader wet AMD population.
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Q B4: What are the current treatments for wet AMD?
A: The current standard treatments for wet AMD primarily involve anti-VEGF therapies, such as Eylea (aflibercept) and Lucentis (ranibizumab). These treatments inhibit VEGF-A to reduce abnormal blood vessel growth and leakage. Eylea acts as a VEGF trap, binding to VEGF-A, VEGF-B, and PlGF (placental growth factor), while Lucentis is a monoclonal antibody fragment that specifically binds to VEGF-A. These treatments are administered through intravitreal injections and have significantly improved visual outcomes for patients with wet AMD.
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Q B5: What are biosimilars, and how do they relate to wet AMD treatment?
A: Biosimilars are biologic medical products that are nearly identical to an original product that is manufactured by a different company. Biosimilars of anti-VEGF therapies like Lucentis are emerging in the market, providing more affordable treatment options for wet AMD. The global market for anti-VEGF therapies, including biosimilars, is substantial, with annual sales exceeding several billion dollars.
Drug Info
Q D1: What is Sozinibercept (OPT-302)?
A: Sozinibercept (OPT-302) is a novel VEGF-C/D inhibitor developed by Opthea to be used in combination with standard anti-VEGF-A therapies for the treatment of wet AMD. By inhibiting VEGF-C and VEGF-D, Sozinibercept aims to reduce vascular leakage and abnormal blood vessel growth, providing a broader spectrum of inhibition compared to existing treatments. Sozinibercept is currently in pivotal Phase 3 trials (COAST and SHORE) for wet AMD.
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Q D2: What is Eylea, and how does it work?
A: Eylea (aflibercept) is an anti-VEGF therapy that acts as a VEGF trap, binding to VEGF-A, VEGF-B, and PlGF (placental growth factor). It is widely used to treat wet AMD by reducing abnormal blood vessel growth and leakage. Eylea is administered through intravitreal injections and has been a cornerstone treatment for wet AMD. The drug generates substantial global revenue, with sales exceeding several billion dollars annually.
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Q D3: What is Lucentis, and how does it work?
A: Lucentis (ranibizumab) is another anti-VEGF therapy that specifically binds to VEGF-A. It is used to treat wet AMD by preventing VEGF-A from promoting abnormal blood vessel growth and leakage. Lucentis is also administered through intravitreal injections and has been a highly effective treatment for wet AMD. Like Eylea, Lucentis contributes significantly to the global market for anti-VEGF therapies.
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Q D4: What are the differences between Sozinibercept and current treatments like Eylea and Lucentis?
A: While Eylea and Lucentis primarily target VEGF-A (and in the case of Eylea, also VEGF-B and PlGF), Sozinibercept (OPT-302) targets VEGF-C and VEGF-D. This broader inhibition aims to provide additional benefits in reducing abnormal blood vessel growth and leakage, particularly in patient sub-groups that are less responsive to VEGF-A inhibition alone. Sozinibercept is designed to be used in combination with these existing treatments to potentially improve visual outcomes for patients with wet AMD.
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